Immunoglobulin (Ig) synthesis in individual lymphocytes is regulated so that only one of a variety of Ig structural genes is expressed. This is seen in heterozygous cells when only one of the two possible light or heavy chain genes is expressed. This phenomenon, allelic exclusion, is known to occur only in lymphocytes; its mechanics are unknown. Other forms of gene selection or gene exclusion are also seen when, in the course of differentiation, the synthesis of one class of Ig is arrested and another class is started. We have found a gene that shows linkage, with a 22 percent crossover frequency, to the kappa light chain gene in rabbits. By determining whether this gene is excluded along with a linked kappa allele in heterozygous cells, we will determine whether exclusion is limited to the Ig chromosome. We have also developed methods that allow us to regulate experimentally the expression of selected Ig genes. One method uses anti-Ig antibody to specifically but reversibly arrest Ig synthesis at or before the initiation of translation. Another method involves the fusion of IgA and IgG synthesizing cells, and the subsequent exclusion of IgG synthesis in some of the fused progeny. We have also developed a cell-free system in which Ig mRNA is made on chromatin and then translated on vesicle-bound ribosomes. Components of repressed and derepressed cells, and of fused cells, their parents, and IgG-repressed progeny, will be analyzed in the cell-free synthesizing system to determine the site and specific mechanism of each regulation event. BIBLIOGRAPHIC REFERENCE: Reiter, H., Hsu, P-L., and Dray, S. (1977) Repression and derepression of IgM synthesis in regulation of the immune system. ICN-UCLA Symposium on Molecular and Cellular Biology. Academic Press, New York (in press).